Saturday, October 4, 2014

Malaria: life cycle

"Humanity has but 3 great enemies: fever, famine and war; of these by far the greatest, by far the most terrible is Fever." William Osler.

Malaria is a protozoan disease transmitted by the bite of infected Anopheles mosquitoes. It is the most important parasitic diseases of humans, with transmission in 103 countries and causing between 1 and 3 million deaths each year. Malaria remains today a heavy burden on tropical communities, a threat to non endemic countries, and a danger to travelers.

Four species of the genus Plasmodium cause nearly all malaria infections in humans. These are P. vivax, P. ovale, P. malariae, P. falciparum.

  1. Human infection begins when a female anopheles mosquito inoculates plasmodium sporozoites from its salivary glands during a blood meal. 
  2. These microscopic motile forms of the malaria parasite are carried rapidly via the blood stream to the liver, where they invade hepatic parenchymal cells and begin a period of asexual reproduction. They areknown as hypnozoites. By this amplification process (known as intra hepatic or preerythocytic schizogony or merogony)
  3. A single sporozoite then produces 10,000 to >30,000 daughter merozoites. 
  4. The swollen liver cell eventually bursts, discharging motile merozoites into the bloodstream.
  5. These then invade the red blood cells and multiply 6-20 fold every 48 to 72 hours.
  6. When parasite densities reach near about 50 per microlitre of blood, the symptomatic stage of infection begins.
  7. In P . vivax and P . ovale infections , a proportion of the hypnozoites lie dormant and do not divide. They can lie dormant from a period of 3 weeks to a year or longer before they begin asexual reproduction. These dormant hypnozoites are the cause of relapses that characterize infection with these 2 species.
  8. After merozoites enter bloodstream they rapidly invade erythrocytes and become trophozoites.
  9. Attachment to erythrocyte is through the a special receptor on the erythrocyte. For P . vivax , this receptor is related to Duffy blood group antigen Fya and Fyb . Therefore west Africans who carry the Duffy fyfy phenotype are resistant to P . vivax malaria.
  10. During early stage of development, the ring stage of 4 parasitic species appear appear similar under microscopy. As trophozoites enlarge, species specific characteristics become apparent. By the end of 48 hour intraerythocytic life cycle (72 hours for P . malariae ), the parasite has consumed nearly all haemoglobin and grown to fill most of the RED and is now called a schizont.
  11. Multiple nuclear divisions take place known as schizogony or merogony and the RBC ruptures to release 6-30 daughter merozoites. These further invade more RBC
  12. After a series of asexual cycles in case of P . falciparum or immediately after release from the liver, in case of the other 3 species , some of the parasites develop into sexual forms called gametocytes that can transmit malaria.
  13. After these gametocytes are ingested by a female anopheles mosquito,  the male female forms form a zygote in the insects midgut. The zygote matures into a ookinete,  which penetrators and encysts in the mosquitos gut wall . the resulting oocyte enlarges until it burns to release  a large number of motile sporozoites.

No comments:

Post a Comment